Muscle Invasive Bladder Cancer (MIBC)Phase 2NCT07201675
Vedisertib (RC48/ADC) Combined With Toripalimab in Bladder-preserving Treatment
A Phase 2 study testing RC48-ADC combined with toripalimab for bladder-sparing therapy in people with Muscle Invasive Bladder Cancer (MIBC), run by Qilu Hospital of Shandong University.
Trial summary
This is a phase II clinical study to evaluate the efficacy of RC48-ADC combined with toripalimab bladder-sparing therapy. The RC48-ADC dose in this study is 2.0 mg/kg Q2W and toripalimab is 3 mg/kg Q2W. This study plans to enroll 59 participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle Invasive Bladder Cancer (MIBC)
- What is being tested?
- RC48-ADC combined with toripalimab for bladder-sparing therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2025to 30 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily agree to participate in the study and sign the informed consent form;
- Male or female, age ≥ 18 years;
- Expected survival ≥ 18 months;
- Pathological and imaging diagnosis of cT2-4aN0M0MIBC;
- Subjects are able to provide specimens of tumor primary lesions detected by PD-L1 and HER2; HER2 IHC 1 or 2 or 3 ;
- No previous systemic therapy;
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- ECOG performance status score of 0 or 1 point;
- Adequate cardiac, bone marrow, liver, and renal function (based on normal values at the study center):
- Left ventricular ejection fraction ≥50%;
- Hemoglobin ≥9 g/dL;
- Absolute neutrophil count (ANC) ≥ 1.5×109/L;
- Platelets≥ 100 ×109/L;
- In patients without liver metastasis, serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN); Blood in liver metastases
- Clear total bilirubin ≤3× ULN
- ALT and AST ≤2.5 × ULN in the absence of liver metastases, ALT and AST≤5 × ULN in the presence of liver metastases;
- Serum creatinine ≤1.5× ULN;
- For female subjects: should be zsurgically sterile, postmenopausal patients, or agree to use at least one medically approved contraceptive measure (such as intrauterine device [IUD], birth control pills, or condoms) during the study treatment period and for 6 months after the end of the study treatment period, must have a negative serum or urine pregnancy test within 7 days prior to study enrollment, and must be non-lactating. Male subjects should agree to use at least one medically approved contraceptive measure (such as condoms, abstinence, etc.) during the study treatment period and within 6 months after the end of the study treatment period;
- Willing and able to comply with trial and follow-up procedures.
Who cannot join
- History of malignant tumors other than urothelial carcinoma, except for the following two conditions:
- Patients have received potentially curative therapy and no evidence of the disease within 5 years;
- Successfully undergoing resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, and other carcinomas in situ;
- Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.);
- Previous allogeneic stem cell or parenchymal organ transplantation; Patients who have received other anti-tumor systemic therapy (including traditional Chinese medicine with anti-tumor indications) in the past, less than 4 weeks after the completion of treatment to before the use of this study, or who have not recovered to ≤ CTCAE grade 1 (except for alopecia and pigmentation);
- Previous or current congenital or acquired immunodeficiency disease;
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- Active or previous documented autoimmune or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment, etc.), vitiligo or asthma that has been completely resolved in childhood, and those who do not need any intervention in adulthood can be included;
- Use of systemic immunosuppressive drugs within 2 weeks prior to enrollment, or anticipation of need for systemic immunosuppressive drugs during the study, except for the following:
- intranasal, inhaled, topical, or local injections (such as intra-articular injections) corticosteroids;
- Systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or other equivalent effects;
- prophylactic use of corticosteroids for hypersensitivity;
- Patients have a known or suspected history of allergy to vidicitumab, anti-PD-1 drugs, or a history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergic to the excipients of the study drug;
- Thrombotic or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.;
- Patients at risk of severe bleeding evaluated by doctors, including but not limited to severe bleeding (bleeding within 3 months> 30 ml), hemoptysis (bleeding within 4 weeks> 5 ml), if the above conditions occur, gastroscopy/evaluation can be performed, and the microscopic evaluation shall prevail; or have active bleeding or abnormal coagulation function, have a bleeding tendency or are receiving thrombolytic, anticoagulant or antiplatelet therapy;
- Significant clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within the past 6 months, congestive heart failure (NYHA classification> of the New York Heart Association Grade 2), poorly controlled or arrhythmias requiring pacemaker therapy, hypertension that cannot be controlled by medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg);
- Other significant clinical and laboratory abnormalities that the investigator believes to affect the safety evaluation, such as: uncontrollable diabetes, chronic kidney disease, grade II or above peripheral neuropathy (CTCAE V5.0), abnormal thyroid function, etc.;
- Serious infection in the active phase or poorly controlled clinically; Active infection, including:
- HIV (HIV) (HIV1/2 antibody) positive;
- Active hepatitis B (HBsAg positive or HBV DNA>2000IU/ml with abnormal liver function);
- Active hepatitis C (positive HCV antibody or HCV RNA ≥103 copies/ml with abnormal liver function);
- Active tuberculosis;
- Other uncontrollable active infections (CTCAE V5.0 >2);
- Not yet recovered from surgery, such as unhealed incisions or serious postoperative complications;
- Pregnant or lactating women, as well as female or male patients of childbearing potential who are unwilling or unable to take effective contraceptive measures;
- Other conditions that the investigator deems unsuitable for inclusion.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
This is a phase II clinical study to evaluate the efficacy of RC48-ADC combined with toripalimab bladder-sparing therapy.
The RC48-ADC dose in this study is 2.0 mg/kg Q2W and toripalimab is 3 mg/kg Q2W.
Read more
This study plans to enroll 59 participants. The participants will start drug therapy within 2 weeks after the first diagnostic resection in the first stage, receiving RC48-ADC combined with toripalimab 3 times. At the 8th week after enrollment, the second stage of cystectomy was performed, and RC48-ADC combined with toripalimab was treated every two weeks thereafter for a total of 3 treatments. After the completion of the two-stage treatment, the participants should be discharged from the group by cystoscopy or other imaging examinations. On the contrary, if the participants have complete remission or partial remission, continue to the third stage of treatment, that is, receive RC48-ADC combined with toripalimab every two weeks for a total of 6 treatments, followed by cystoscopy, imaging, or a third cystectomy. If the participants achieve complete remission of the disease, maintenance immunotherapy will be given for 12 months. If the participants show that there is still a tumor, the participants will be discharged from the group for other treatments. Due to disease progression, death, participants voluntarily requested termination of study treatment, toxicity intolerance, initiation of new anti-tumor therapy, pregnancy, serious violation of the study process stipulated by the protocol, termination of study treatment determined by the investigator based on the best interests of the participants, loss to follow-up, whichever occurred first.
During the study, the first and second electrotoxic tissues were sequenced using RNA and single-cell sequencing, and ctDNA was tested in urine before treatment, in the third month, and in the sixth month.
- Conditions
- Muscle Invasive Bladder Cancer (MIBC)
- Being tested
- RC48-ADC combined with toripalimab for bladder-sparing therapy
- Keywords
- RC48, muscle invasive bladder cancer, Toripalimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RC48-ADC combined with toripalimab for bladder-sparing therapyDrug
RC48-ADC combined with toripalimab for bladder-sparing therapy
| Study group | Role | What they receive |
|---|---|---|
| RC48-ADC combined with toripalimab for bladder-sparing therapy | Experimental | Not described Receives: Drug: RC48-ADC combined with toripalimab for bladder-sparing therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
cCR (Clinical Complete response)
Measured: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
Secondary outcomes (4)
OS (Overall Survival)
Measured: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
DFS (Disease Free Survival)
Measured: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
cPR (Clinical Partial Response)
Measured: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
Barthel Index
BI (Barthel Index), 0-100 score. The higher the score, the stronger the ability to take care of oneself.
Measured: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2025
- Study start1 Dec 2025 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Muscle Invasive Bladder Cancer (MIBC)Studies of the same condition, open and under way.
- More trials run by Qilu Hospital of Shandong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07201675
- Sponsor's protocol ID
- CSZ05
- Status last verified
- Aug 2025
- First submitted
- 7 Sep 2025
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Sheng X, Wang L, He Z, Shi Y, Luo H, Han W, Yao X, Shi B, Liu J, Hu C, Liu Z, Guo H, Yu G, Ji Z, Ying J, Ling Y, Yu S, Hu Y, Guo J, Fang J, Zhou A, Guo J. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. J Clin Oncol. 2024 Apr 20;42(12):1391-1402. doi: 10.1200/JCO.22.02912. Epub 2023 Nov 21.
PubMed 37988648Wang J, Liu Y, Zhang Q, Li W, Feng J, Wang X, Fang J, Han Y, Xu B. Disitamab vedotin, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpression and HER2-low advanced breast cancer: a phase I/Ib study. Cancer Commun (Lond). 2024 Jul;44(7):833-851. doi: 10.1002/cac2.12577. Epub 2024 Jun 28.
PubMed 38940019Sheng X, Chen H, Hu B, Yao X, Liu Z, Yao X, Guo H, Hu Y, Ji Z, Luo H, Shi B, Liu J, Wu J, Zhou F, He Z, Fan J, Wang W, Feng H, Yao S, Keegan P, Huang Y, Guo J. Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03. Clin Cancer Res. 2022 Feb 1;28(3):489-497. doi: 10.1158/1078-0432.CCR-21-2210. Epub 2021 Nov 5.
PubMed 34740921
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vedisertib (RC48/ADC) Combined With Toripalimab in Bladder-preserving Treatment
- ClinicalTrials.gov ID
- NCT07201675
- Acronym / sponsor ID
- CSZ05
- Conditions
- Muscle Invasive Bladder Cancer (MIBC)
- Keywords
- RC48, muscle invasive bladder cancer, Toripalimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 59 participants (estimated)
- Lead sponsor
- Qilu Hospital of Shandong UniversityUniversity, hospital or other
- Study start
- 1 Dec 2025 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 1 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II clinical study to evaluate the efficacy of RC48-ADC combined with toripalimab bladder-sparing therapy.
The RC48-ADC dose in this study is 2.0 mg/kg Q2W and toripalimab is 3 mg/kg Q2W.
This study plans to enroll 59 participants. The participants will start drug therapy within 2 weeks after the first diagnostic resection in the first stage, receiving RC48-ADC combined with toripalimab 3 times. At the 8th week after enrollment, the second stage of cystectomy was performed, and RC48-ADC combined with toripalimab was treated every two weeks thereafter for a total of 3 treatments. After the completion of the two-stage treatment, the participants should be discharged from the group by cystoscopy or other imaging examinations. On the contrary, if the participants have complete remission or partial remission, continue to the third stage of treatment, that is, receive RC48-ADC combined with toripalimab every two weeks for a total of 6 treatments, followed by cystoscopy, imaging, or a third cystectomy. If the participants achieve complete remission of the disease, maintenance immunotherapy will be given for 12 months. If the participants show that there is still a tumor, the participants will be discharged from the group for other treatments. Due to disease progression, death, participants voluntarily requested termination of study treatment, toxicity intolerance, initiation of new anti-tumor therapy, pregnancy, serious violation of the study process stipulated by the protocol, termination of study treatment determined by the investigator based on the best interests of the participants, loss to follow-up, whichever occurred first.
During the study, the first and second electrotoxic tissues were sequenced using RNA and single-cell sequencing, and ctDNA was tested in urine before treatment, in the third month, and in the sixth month.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RC48-ADC combined with toripalimab for bladder-sparing therapy | Experimental | Drug: RC48-ADC combined with toripalimab for bladder-sparing therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Voluntarily agree to participate in the study and sign the informed consent form;
- Male or female, age ≥ 18 years;
- Expected survival ≥ 18 months;
- Pathological and imaging diagnosis of cT2-4aN0M0MIBC;
- Subjects are able to provide specimens of tumor primary lesions detected by PD-L1 and HER2; HER2 IHC 1 or 2 or 3 ;
Key exclusion criteria (25 listed)
- History of malignant tumors other than urothelial carcinoma, except for the following two conditions:
- Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.);
- Previous allogeneic stem cell or parenchymal organ transplantation; Patients who have received other anti-tumor systemic therapy (including traditional Chinese medicine with anti-tumor indications) in the past, less than 4 weeks after the completion of treatment to before the use of this study, or who have not recovered to ≤ CTCAE grade 1 (except for alopecia and pigmentation);
- Previous or current congenital or acquired immunodeficiency disease;
- Active or previous documented autoimmune or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment, etc.), vitiligo or asthma that has been completely resolved in childhood, and those who do not need any intervention in adulthood can be included;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RC48-ADC combined with toripalimab for bladder-sparing therapyRC48-ADC combined with toripalimab for bladder-sparing therapy | Drug | RC48-ADC combined with toripalimab for bladder-sparing therapy |
Primary outcome
cCR (Clinical Complete response)
Time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
4 secondary outcomes
OS (Overall Survival)
Time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
DFS (Disease Free Survival)
Time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
cPR (Clinical Partial Response)
Time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
Barthel Index
Time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Results publication: PubMed 37988648Sheng X, Wang L, He Z, Shi Y, Luo H, Han W, Yao X, Shi B, Liu J, Hu C, Liu Z, Guo H, Yu G, Ji Z, Ying J, Ling Y, Yu S, Hu Y, Guo J, Fang J, Zhou A, Guo J. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. J Clin Oncol. 2024 Apr 20;42(12):1391-1402. doi: 10.1200/JCO.22.02912. Epub 2023 Nov 21.
- Results publication: PubMed 38940019Wang J, Liu Y, Zhang Q, Li W, Feng J, Wang X, Fang J, Han Y, Xu B. Disitamab vedotin, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpression and HER2-low advanced breast cancer: a phase I/Ib study. Cancer Commun (Lond). 2024 Jul;44(7):833-851. doi: 10.1002/cac2.12577. Epub 2024 Jun 28.
- Results publication: PubMed 34740921Sheng X, Chen H, Hu B, Yao X, Liu Z, Yao X, Guo H, Hu Y, Ji Z, Luo H, Shi B, Liu J, Wu J, Zhou F, He Z, Fan J, Wang W, Feng H, Yao S, Keegan P, Huang Y, Guo J. Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03. Clin Cancer Res. 2022 Feb 1;28(3):489-497. doi: 10.1158/1078-0432.CCR-21-2210. Epub 2021 Nov 5.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RC48-ADC combined with toripalimab for bladder-sparing therapy in people with Muscle Invasive Bladder Cancer (MIBC), run by Qilu Hospital of Shandong University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shouzhen Chen, doctor (+8618560089085, chenshouzhen@email.sdu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cCR (Clinical Complete response) (time frame: From date of randomization, follow-up once every 12 weeks until the date of first documented death, loss to follow-up, withdrawal of informed consent, whichever came first, assessed up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07201675, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.